A central problem in cancer research is determining the structure of membranes in normal and tumor cells. Conventional transmission and scanning electron microscopy investigations in a number of laboratories are contributing to our knowledge of cell surface topography, but it is clear that fresh approaches are also needed. The purpose of this research project is to develop and apply a new kind of microscopy specifically designed to examine chemical differences in cell surfaces and other membranes. This technique, photoelectron microscopy, utilizes differences in ionization potentials and electron quantum yields to visualize the biological surfaces. The escape depth of the electrons is extremely short, which permits mapping of membrane surfaces without interference from the cytoplasmic contents of the cell. The mechanism of contrast is entirely different from transmission and scanning electron microscopy, and it is possible to visualize different biochemical features. In previous grant periods, the feasibility of this approach has been experimentally verified, the first low magnification images ever seen of biological samples have been reported, and the three main variables (lateral resolution, depth resolution and contrast) have been examined. The main experimental goals during this continuation year are: determining topographical contrast of tissue culture cell surfaces, a search for photoelectron labels, testing whether the photoelectron microscope can detect and map distributions of the aromatic carcinogen benzo(a)pyrene, and parallel instrumental developments aimed at increasing the microscope performance.